Onpattro

Therapy should be initiated under the supervision of a physician knowledgeable in the management of amyloidosis. Posology The recommended dose of Onpattro is 300 micrograms per kg body weight administered via intravenous (IV) infusion once every 3 weeks.

Dosing is based on actual body weight. For patients weighing ≥ 100 kg, the maximum recommended dose is 30 mg. 1). 1). 4). 4). Each of the following medicinal products should be given on the day of Onpattro infusion at least 60 minutes prior to the start of infusion: • Intravenous corticosteroid (dexamethasone 10 mg, or equivalent) • Oral paracetamol (500 mg) • Intravenous H1 blocker (diphenhydramine 50 mg, or equivalent) • Intravenous H2 blocker (famotidine 20 mg, or equivalent) For premedications not available or not tolerated intravenously, equivalents may be administered orally.

5 mg to a minimum dose of 5 mg of dexamethasone (IV), or equivalent. The patient should receive at least 3 consecutive IV infusions of Onpattro without experiencing IRRs before each reduction in corticosteroid premedication. 8). Missed dose If a dose is missed, Onpattro should be administered as soon as possible.

• If Onpattro is administered within 3 days of the missed dose, dosing should be continued according to the patient’s original schedule. • If Onpattro is administered more than 3 days after the missed dose, dosing should be continued every 3 weeks thereafter.

2). 5 x ULN and any AST). 2). 73m2). 2). Paediatric population The safety and efficacy of Onpattro in children or adolescents < 18 years of age have not been established. No data are available. Method of administration Onpattro is for intravenous use.

6). 2 micron polyethersulfone (PES) in-line infusion filter must be used. The infusion sets and lines must be free of di(2- ethylhexyl)phthalate (DEHP). • The diluted solution of Onpattro should be infused intravenously over approximately 80 minutes at an initial infusion rate of approximately 1 mL/min for the first 15 minutes, followed by an increase to approximately 3 mL/min for the remainder of the infusion.

4). • Onpattro must be administered through a free-flowing venous access line. The infusion site should be monitored for possible infiltration during administration. Suspected extravasation should be managed according to local standard practice for non-vesicants.

9%). 7%) discontinued treatment during clinical studies due to an infusion-related reaction. Tabulated list of adverse reactions The adverse reactions are presented as MedDRA preferred terms under the MedDRA System Organ Class (SOC) by frequency.

Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. The frequency of the adverse reactions is expressed according to the following categories: • Very common (≥ 1/10) • Common (≥ 1/100 to < 1/10) • Uncommon ( 1/1 000 to < 1/100) 7 Table 1: Adverse reactions reported for Onpattro 300 micrograms per kg System Organ Class Adverse Reaction Frequency Infections and infestations Bronchitis Common Sinusitis Common Rhinitis Common Immune system disorders Infusion-related reaction Very common Ear and labyrinth disorders Vertigo Common Respiratory, thoracic and mediastinal disorders Dyspnoea Common Gastrointestinal disorders Dyspepsia Common Skin and subcutaneous tissue disorders Erythema Common Musculoskeletal and connective tissue disorders Arthralgia Common Muscle spasms Common General disorders and administration site conditions Peripheral oedema Very common Extravasation Uncommon Description of selected adverse reactions Infusion-related reactions Symptoms of IRRs include, but are not limited to: arthralgia or pain (including back, neck, or musculoskeletal pain), flushing (including erythema of face or skin warm), nausea, abdominal pain, dyspnoea or cough, dysphonia, chest discomfort or chest pain, headache, rash, pruritus, chills, dizziness, fatigue, increased heart rate or palpitations, hypotension which may include syncope, hypertension, facial oedema.

In clinical studies, all patients received premedication with a corticosteroid, paracetamol, and H1 and H2 blockers to reduce the risk of IRRs. 1% of placebo-treated patients. 8%) in severity. 6% experienced the first IRR within the first 2 infusions.

The frequency of IRRs decreased over time. Some patients still experienced IRRs after 18 months of treatment, and in a few patients IRRs continued to be frequent. Few IRRs led to infusion interruption. IRRs resulted in permanent discontinuation of Onpattro in < 1% of patients in clinical studies.

Infusion-related reactions IRRs have been observed in patients treated with Onpattro. 8). Across clinical studies, the most common symptoms (reported in ≥ 2% of patients) of IRRs were flushing, back pain, nausea, abdominal pain, dyspnoea, and headache.

IRRs may also include hypotension and syncope. 2). , corticosteroids or other symptomatic treatment) should be considered, as clinically indicated. If the infusion is interrupted, resumption of the infusion at a slower infusion rate may be considered after symptoms have resolved.

The infusion should be discontinued in the case of a serious or life-threatening IRR. Some patients who experience IRRs may benefit from a slower infusion rate or additional or higher doses of one or more of the premedications with subsequent infusions to reduce the risk of IRRs.

1). Serum vitamin A levels below the lower limit of normal should be corrected and any ocular symptoms or signs due to vitamin A deficiency should be evaluated prior to initiation of treatment. Patients receiving Onpattro should take oral supplementation of approximately 2 500 IU vitamin A per day to reduce the potential risk of ocular toxicity due to vitamin A deficiency.

Referral for ophthalmological assessment is recommended if patients develop ocular symptoms suggestive of vitamin A deficiency, including reduced night vision or night blindness, persistent dry eyes, eye inflammation, corneal inflammation or ulceration, corneal thickening or corneal perforation.

5). During the first 60 days of pregnancy, both too high or too low vitamin A levels may be associated with an increased risk of foetal malformation. Therefore, pregnancy should be excluded before initiating Onpattro and women of childbearing potential should practise effective contraception.

If a woman intends to become pregnant, Onpattro and vitamin A supplementation should be discontinued, and serum vitamin A levels should be monitored and have returned to normal before conception is attempted. 6). Vitamin A supplementation should be discontinued during the first trimester, unless the pregnant woman has clinical signs of vitamin A deficiency.

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